| Recently, the incidence of cardiovascular disease has been rapidly increased in the clinic. In the modern society the phenomena of stress has regaded as the most important factor that forming the process of hypertension. Effective treatments of hypertension are still not been totally remarked due to the unknown clear etiological factors. So it is very important to find the effective required medicine that can cure the pathogenesis of this disease. Pregnanolone (PGN), which is reported as one of the neurosteroids, in the mammalian has been founded to be secreted at different body tissues as well as the central nervous system (C.N.S). It is also been reported that the neurosteroids exert many functions such as relieve of pain and anti-stress actions, in addition they can show increased concentrations in both blood and brain following stress. So PGN may play an inhibitory role in the process of stress-induced hypertension (SIH) in rats by anti-stress actions. It has been proved that PGN can activate GABAA receptor complex, resulting in the opening of its central chloride channel, which lead to hyperpolarization of the plasma membrane and inhibition of further neuronal firing. On the other hand, our previous study has shown habenula nucleus (Hb), the paraventricular nucleus (PVN) and the central nucleus of amgydaloid (CeA) play an important role in the stess reactions. PGN and its receptors can be distributed vastly in CNS, especially in the central cardiovascular system. Therefore, in the present study, the effects of PGN on blood pressure (BP) and unit discharges of Hb in stress-induced hypertension have been investigated in rat. The purpose of the present study is to explore the action and its central mechanisms of PGN in the etiology of stress hypertension in rats by using electryphysiology technique.1. The effect of PGN on the tail artery systolic presure, agniotension II (AII) levels, and c-fos in rat during stimulation.Applying electric shock to animal feet together with a noise simulus established SIH rat model. PGN was administered intraperitoneally at 0.24 mg/kg/d and blood pressure, AII levels, and expression of Fos-like protein immunoreactive (FLI) neurons in the brain areas has been determined. Rats were randomly divided into five groups: 1) control group, 2) stressed group for 1 h, 3) stressed group for 1 h after PGN pre-treatment, 4) stressed group for a 2 h session, twice a day, for 15 days, and 5) stressed group for a 2 h session after PGN pre-treatment, twice a day, for 15 days. The results showed that increased systolic pressure of tail artery caused by a 15 days stress treatment was significantly reduced by PGN pre-treatment (P<0.001). AII levels, measured as radioactive immunoreactivity, were significantly elevated (p<0.001) after the rats were stressed for 1 h or 15 days, which were significantly reduced by PGN treatment in both stress levels (p<0.05). Only a small number of FLI neurons were founded in the brain areas of the control group, 15 days stress group, and 15 days stress with PGN group. The 1 h stress group had markedly more FLI neurons in the lateral habenular nucleus and the medial habenular nucleus, the paraventricular nucleus, the central nucleus of amgydaloid and the lateral hypothalamus compared to control group. PGN pretreatment significantly prevented the increase in the number of FLI neurons. These results indicated that PGN pretreatment prevents elevated tail artery systolic pressure in SIH rats, and this effect of PGN may be mediated through reducing AII levels and inhibiting the activity of cardiovascular center which involved in stress.2 Effect of microinjection of PGN into PVN, Hb and the lateral cerebral ventricle on the Cardiovascular Response in SIH and normal rats Arterial blood pressure (BP) and heart rate (HR) were monitored following injection of PGN into the lateral cerebral ventricle PVN and Hb in normal and SIH rats. Results icv of PGN could induce a decrease of BP in normal and SIH rats, respectively. The effects of PGN on blood press...
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